In this competing renewal application Dr. Luster proposes to study the role of the chemokine IP-10 in T cell recruitment and disease. The first aim is to determine the structural domains on IP-10 that mediate its chemotactic effects on T cells, as well as its anti-proliferative effects on endothelial cells. Solving the crystal structure of IP-10 is part of this aim. The second aim is to determine the roles of IP-10 and CXCR3 in murine models of inflammation and infection. Both IP-10 and CXCR3 knockout mice will be used in these studies. The third aim is to correlate the expression of IP-10 with the infiltration of CXCR3+ T cells in tissues isolated from patients with several selected diseases.